突变TDP43诱导神经元兴奋性升高以及双甲氧姜黄素的神经保护作用

Hyperexcitability of neurons due to mutant TDP43 and the protective effect of dimethoxy curcumin

目的观察稳定表达Q331K突变TDP43、人野生型(WT)TDP43和空质粒(对照)的运动神经元样细胞(NSC34)动作电位的特性,评价TDP43突变对兴奋性的影响,测定双甲氧姜黄素(DMC)对细胞保护作用。方法采用全细胞膜片钳技术记录Q331K组、WT组和对照组三类细胞的动作电位。结果 Q331K组细胞动作电位频率明显增高,阈电位明显降低(p<0.05;p<0.01)。给予15!mol/L DMC培养24h后,这三类细胞表现出相同水平的动作电位频率和阈电位;与给药前比较,Q331K细胞动作电位频率明显下降、阈电位明显升高,而WT和对照细胞没有明显变化。结论 Q331K突变的TDP43诱导NSC34细胞呈现高兴奋性水平,DMC可抑制TDP43突变所诱导的细胞高兴奋性。

Objective To estimate the effect of mutated TDP43 on excitability of motoneuron-like cells （NSC34） , we plan to observe properties of action potentials in NSC34 cells expressing stably mutant Q331K TDP43, human wild-type TDP43 （WT） or empty vector （control）, and examine the protective influence of dimethoxy cureumin （DMC） on neurons.Methods Whole-cell patch clamp was used to record action potentials in Q331K, WT and control cells. Results The frequency of action potential enhances obviously and the threshold decreases significantly in Q331K cells （p〈0.05 or p〈0.01）. After euhured with 15 μmoL/L DMC for 24 hours, frequency and threshold of action potential are shown at the same level in the three-type cells. Compared with values before DMC treatment, frequency of action potentials drops obviously and threshold rises significantly, and there are no significant changes in WT and control cells.Conclusion Mutant Q331K TDP43 can induce hyperexcitability in NSC34 cells, and DMC protects neurons from damages through inhibition of high excitability due to mutant TDP43.